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4-phenyl-6-(2,2,2-trifluoro-1-phenylethoxy)pyrimidine-based compounds and methods of their use

a technology of pyrimidine and phenyl-6, which is applied in the field of 4-phenyl-6(2,2,2-trifluoro-1-phenylethoxy) pyrimidine-based compounds, can solve the problems that drugs affecting serotonin receptors are often attended by adverse effects

Active Publication Date: 2009-06-30
TERSERA THERAPEUTICS LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Because serotonin is involved in so many biochemical processes, drugs that affect serotonin receptors are often attended by adverse effects.

Method used

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  • 4-phenyl-6-(2,2,2-trifluoro-1-phenylethoxy)pyrimidine-based compounds and methods of their use

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Embodiment Construction

[0012]This invention is based, in part, on the discovery that knocking out the tph1 gene in mice significantly reduces levels of GI serotonin, yet causes little, if any, measurable effect on the central nervous system (CNS).

[0013]This invention is also based on the discovery of compounds that inhibit TPH (e.g., TPH1). When administered to mammals, preferred compounds of the invention reduce serotonin levels, have pharmacokinetic and pharmacodynamic properties that enable their practical use for the treatment, prevention and management of diseases and disorders, and have a broad safety margin between pharmacological effect and toxicity or unfavorable side reactions.

5.1. DEFINITIONS

[0014]Unless otherwise indicated, the term “alkenyl” means a straight chain, branched and / or cyclic hydrocarbon having from 2 to 20 (e.g., 2 to 10 or 2 to 6) carbon atoms, and including at least one carbon-carbon double bond. Representative alkenyl moieties include vinyl, allyl, 1-butenyl, 2-butenyl, isobut...

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Abstract

Compounds of formula I are disclosed, as well as compositions comprising them and methods of their use to treat, prevent and / or manage diseases and disorders:

Description

[0001]This application claims priority to U.S. provisional application No. 60 / 874,596, filed Dec. 12, 2006, the entirety of which is incorporated herein by reference.1. FIELD OF THE INVENTION[0002]This invention relates to 4-phenyl-6-(2,2,2-trifluoro-1-phenylethoxy)pyrimidine-based compounds, compositions comprising them, and their use in the treatment, prevention and management of diseases and disorders.2. BACKGROUND[0003]The neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] is involved in multiple central nervous facets of mood control and in regulating sleep, anxiety, alcoholism, drug abuse, food intake, and sexual behavior. In peripheral tissues, serotonin is reportedly implicated in the regulation of vascular tone, gut motility, primary hemostasis, and cell-mediated immune responses. Walther, D. J., et al., Science 299:76 (2003).[0004]The enzyme tryptophan hydroxylase (TPH) catalyzes the rate limiting step of the biosynthesis of serotonin. Two isoforms of TPH have been re...

Claims

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Application Information

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Patent Type & Authority Patents(United States)
IPC IPC(8): C07D239/34A61K31/506C07D403/12A61P9/02
CPCC07D239/34C07D401/12C07D403/12C07D405/12A61K31/506C07D413/12C07D417/12C07D409/12A61K31/4152A61P1/00A61P1/04A61P1/06A61P1/08A61P1/10A61P1/12A61P1/16A61P1/18A61P11/00A61P11/08A61P17/00A61P21/00A61P25/08A61P25/20A61P25/22A61P25/24A61P35/00A61P43/00A61P9/00A61P9/02A61P9/12A61P3/10
Inventor DEVASAGAYARAJ, AROKIASAMYJIN, HAIHONGSHI, ZHI-CAITUNOORI, ASHOKWANG, YINGZHANG, CHENGMIN
Owner TERSERA THERAPEUTICS LLC
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